Quinine (thing)

For most of human history, those who inhabited wet areas in warm climates lived in terror of a frightful illness which the classical Romans called 'Swamp Fever.' It struck quickly, wracking the patient with high fevers and dreadful, prolonged weakness. Anyone who chanced to survive was almost certain to be cursed with recurring bouts of the disease for the rest of their lives. The bark of an obscure evergreen tree from South America changed all of that.

Variously known as quinidine, quinia, quinina, quinuina, Peruvian bark, and Jesuits' bark, the alkaloid salts derived from the cinchona tree of the Andes mountains were the first botanical by-product ever used in long-term medical chemotherapy. Quinine's action against malaria was known to people of the region for centuries, and the introduction of quinine to Europe in the 17th century by Jesuitmissionaries alleviated the fear of this deadly scourge and allowed for colonial expansion into tropical areas of the Americas, Africa and Southeast Asia. This must surely rank quinine as one of the most important plant derivatives in history

1638, the New World—a young countess is stricken with deadly malaria. Her enterprising personal physician, Dr. Juan de Vega had heard tales of an amazing 'fever tree' growing high in the mountains. Obtaining some of the bark of this amazing plant, he treated her and the Countess of Chichon became the first European on record to receive quinine. Her health much improved, the Countess championed the use of this medicine in the fever-ridden lands surrounding her husband's estate southeast of Madrid. The medicine-bearing tree was dubbed cinchona in her honor. For his part, the doctor, who was a bit of an opportunist, imported the bark to Europe and made a modest fortune.

Malaria, and the fear thereof, has been a dark shadow across the mind of people since prehistoric times. The mechanics of the transmission of the disease (and the role mosquitoes play in it) remained unknown, but the consequences were depressingly familiar, particularly to anyone living in a tropical or subtropical region. As late as the 19th century, most doctors believed that malaria was caused by breathing the unhealthy miasmas associated with swamps and standing water (thus the name: Italian, mala, 'bad' and aria, 'air'). Many sub-Saharan African people were resistant to the disease, but European colonists had a very tough time establishing a foothold in tropical areas—the terrifying prospect of malaria also kept the wetlands of Europe and the Americas sparsely populated until the introduction of quinine.

The Jesuits were the friends and protectors of the Peruvian natives and thus the Society of Jesus had something of an advantage in obtaining the bark. As many Protestants had no love for the Jesuits, many referred to quinine as the "powder of the devil" and refused the cure. Some, including Oliver Cromwell, died rather than accept the treatment.

Despite Protestant protests, use of the bark spread rapidly. As a result, many stands of cinchona were being chopped down even though the Jesuits were attempting to replant the trees as quickly as they were being removed. The sad irony about all of this is that the amount of the alkaloid varies wildly—both as a function of the species and variety of the tree, and even of the elevation at which it is grown, so much of the clear-cutting was completely useless. The deforestation, coupled with severe political instability in the region (where a small handful of countries endured 43 revolutions in the 30 years between 1820 and 1850) was turning quinine into a very precious commodity.

European physicians eventually discovered the best way to deliver the medicine. Cinchona bark was heated in white wine, the resultant slurry was strained and the tincture was given to the patient. This method was used until better methods of chemical analysis made it possible for scientists to isolate the alkaloids from the bark.

It took an army of researchers, working with primitive methods and equipment, to unlock the secret of the bark. By the 1820s, researchers in France had isolated the medicinal compound from the bark. The scientists called the compound quinine from the native name quina, meaning, roughly, 'tree bark.' By the mid 1850s, standards were set for determining the effectiveness of cinchona bark. As it turns out, four closely-related alkaloids exist in the bark (quinine, cinchonine, quinidine and cinchonidine, in case you are keeping score), but the most effective of the four was called quinine, and so the raw mixture also kept that name.

In order to meet the burgeoning demand for this drug, the English government decided to cultivate the cinchona in India. With the help of Clement Markham, an eminent amateur explorer, geographer and world traveler, specimens were secured—by the mid-1860s, England's cinchona plantations were up and running. The enterprising Dutch were not far behind, planting in Java, investing heavily and eventually making a vast sum of money (something the Dutch did exceptionally well at the time).

With the availability of inexpensive quinine, the population of India boomed. Labor was exported all over the British Empire and the population demographics of those colonies changed dramatically (many of these populations are still in evidence in England and in the former colonies—and this is part of the reason that you can buy vindaloo in almost any corner of the English-speaking world).

Organic chemistry came into its own as a science in the nineteenth century: dye, synthetic textiles and materials, fertilizer and pharmaceuticals were all being created in the laboratory. Making a synthetic version of quinine seemed an impossible quest for a very long time, at least until the course of the disease was better understood. The work of the great parasitologist Paul Erlich, who identified a synthetic treatments for syphilis and trypanosomiasis, laid the groundwork for understanding malaria, and thus for finding a synthetic treatment. The first artificial quinine substitute, Pamaquin, became available in 1926.

Quinine and Malaria

For centuries, quinine was the only treatment for malaria. The drug does not actually cure malaria—the mechanism is not fully understood, but it appears to interfere with the metabolic processes of one stage of the parasitic organism responsible for the disease. This destroys all parasites that are at that stage of their life cycle, but the patient's body will still contain more parasites. Thus, a person treated with quinine will still suffer from low levels of malaria, but the damage and symptoms are greatly reduced. Quinine is also a powerful treatment for fever and was occasionally used (in dangerously high dosages) to abort pregnancies.

Quinine has a number of drawbacks which make it a bit less than ideal as a treatment: it is horribly bitter stuff, and it was taken orally—not a pleasant prospect over the long term. In doses greater than 25 milligrams per kilogram of body weight, quinine salts may cause a form of poisoning called cinchonism or quininism. Acute quinine poisoning usually results in headache, nausea and rashes; in extreme cases, it may lead to blindness, heart failure or coma. Long-term use of quinine may be hazardous, particularly in large doses; effects may include severe hearing loss or tinnitus, loss of weight or appetite, and hypoglycemia. Prolonged quinine use may also increase the chances of contracting the potentially fatal disease known as blackwater fever.

Because of its drawbacks, and the fact that some strains of malaria have developed resistance to quinine, it is not widely used in the treatment of the disease these days.
More sophisticated drugs (many of them based on quinine) such as chloroquine and mefloquine are available, the side effects lessened or removed. In a pinch, however, the bark may still be tinctured and ingested as it was in ages past. In addition to treatment for malaria, quinine is sometimes used for the reduction of fever, anti-bacterial agent, an analgesic, and as a muscle relaxant (especially in the case of persistent acute cramping). It is also used as a flavour in tonic water, giving the classy, sassy gin and tonic its distinctive taste and aroma.